Role of the pre-supplementary motor area (pre-SMA) in the overcoming of automatic eye movements: Preceding data from our and other laboratories have suggested that a part of the medial frontal cortex called the pre-SMA plays an important role in changing action plans or task switching. We hypothesized that the pre-SMA plays a role in generating desired motor acts in situations where the selection of action based on automatic processes is unfavorable. To test this hypothesis, we recorded neuronal activity in the pre-SMA of a monkey performing a saccade task in which the monkey had to occasionally switch from automatic to controlled behavior. We found that, during a presaccadic period, many pre-SMA cells selectively changed their firing on color-switch trials. When we electrically microstimulated the pre-SMA at cue onset, the correct rate on switch trials increased significantly. These data support our hypothesis that the pre-SMA plays a key part in the overcoming of automatic action generation to initiate a newly required action. We are currently testing an extended hypothesis that the pre-SMA executes its switching function through its projection to the basal ganglia.? ? Role of the primate lateral habenula in negative motivational control of oculomotor behavior: Although the absence of dopamine in the striatum leads to severe deficits in body movements as seen in Parkinsons disease, recent studies indicate that dopamine neurons carry reward-related, not movement-related, signals. However, it was unclear which parts of the brain provide dopamine neurons with signals necessary for these actions. We hypothesized that the lateral habenula is an important source of the reward signals. To test this hypothesis, we recorded the activity of habenula neurons and dopamine neurons while monkeys were performing a visually guided saccade task with positionally biased reward outcomes. A majority of habenula neurons were excited by a noreward-predicting target and inhibited by a reward-predicting target. In contrast, dopamine neurons were excited and inhibited by reward-predicting and noreward-predicting targets, respectively. Each time the rewarded and unrewarded positions were reversed, both habenula and dopamine neurons reversed their responses as the bias in saccade latency reversed. In unrewarded trials, the excitation of habenula neurons started earlier than the inhibition of dopamine neurons. Furthermore, weak electrical stimulation inside, not outside, the habenula elicited strong inhibitions in dopamine neurons. These results suggest that the lateral habenula guides the basal ganglia to suppress less rewarding saccadic eye movements by inhibiting dopamine neurons.
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